PC 4 is a promising second generation photosensitizer for photodynamic therapy (PDT) that is now in Phase clinical trials for the treatment of cutaneous T cell lymphoma (CTCL), basal cell carcinoma (BCC) and cutaneous metastases. Other clinical trials are in early planning stages at Case Western Reserve University. PC 4 has excellent photophysical characteristics, including an intense extinction at 670 nm, where light penetration in tissue is efficient, and high singlet oxygen quantum yield. Biological responses to PC 4-PDT have been extensively characterized by researchers at Case with support of the National Cancer Institute. NCI also sponsored all of the preclinical IND (Investigational New Drug)-directed studies and provides GMP (Good Manufacturing Practices) PC 4 for the clinical trials. Thus, there has been a significant scientific and financial investment in PC 4. Initial experience in the Phase I trial has been positive, however it has also underscored the urgent need for optical dosimetry and monitoring in order to make rational treatment planning decisions. The outcome of PDT depends on the availability of sensitizer and light throughout the lesion, and the singlet oxygen mechanism of PC 4-PDT requires oxygen. None of these ingredients can be assumed and must therefore be measured directly or indirectly. Optical reporters of the deposition of photodynamic dose and/or biological response are also desirable. Special problems and opportunities present themselves in the particular case of PC 4. For example, because of its extremely high extinction at the treatment wavelength, PC 4 in the tissue may influence the transport of light. To address these dosimetry and monitoring issues in close connection to ongoing and planned clinical trials, we propose the following specific aims: (1) to construct and characterize an optical system capable of delivering PDT irradiation and performing, both fluorescence and reflectance spectroscopy in CTCL and BCC patients;(2) to evaluate the irradiation-induced increase in PC 4 fluorescence as a possible dose metric in vivo;(3) to evaluate light scattering as a means of reporting mitochondria! responses to PC 4-PDT in vivo;and (4) to investigate the kinetics and intratumor distribution of PC 4 following intratumor injection and to establish the efficacy of this route of administration. Relevance to public health: Photodynamic therapy is being tested for the treatment of several cutaneous diseases. Research proposed here will develop means for measuring the quantities that determine the outcome of this therapy. Results will contribute to the ongoing clinical trials.